The Journal of Neuroscience, December 31, 2008, 28(53):14358-14362; doi:10.1523/JNEUROSCI.4973-08.2008
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Brief Communications
Differential cAMP Signaling at Hippocampal Output Synapses
Christian Wozny,1 *
Nikolaus Maier,1 *
Pawel Fidzinski,2,3
Jörg Breustedt,1
Joachim Behr,2,3 * and
Dietmar Schmitz1 *
1Neuroscience Research Center, 2Department of Psychiatry and Psychotherapy, and 3Johannes Müller Institute of Physiology, Charité–Universitätsmedizin Berlin, 10117 Berlin, Germany
Correspondence should be addressed to either of the following: Christian Wozny at his present address: Medical Research Council Laboratory of Molecular Biology, Hills Road, Cambridge CB2 OQH, UK, Email: cwozny{at}mrc-lmb.cam.ac.uk; or Dietmar Schmitz, Neuroscience Research Center, Charité–Universitätsmedizin Berlin, Charitéplatz 1, 10117 Berlin, Germany, Email: dietmar.schmitz{at}charite.de
cAMP is a critical second messenger involved in synaptic transmission and synaptic plasticity. Here, we show that activation of the adenylyl cyclase by forskolin and application of the cAMP-analog Sp-5,6-DCl-cBIMPS both mimicked and occluded tetanus-induced long-term potentiation (LTP) in subicular bursting neurons, but not in subicular regular firing cells. Furthermore, LTP in bursting cells was inhibited by protein kinase A (PKA) inhibitors Rp-8-CPT-cAMP and H-89. Variations in the degree of EPSC blockade by the low-affinity competitive AMPA receptor-antagonist
-D-glutamyl-glycine (
-DGG), analysis of the coefficient of variance as well as changes in short-term potentiation suggest an increase of glutamate concentration in the synaptic cleft after expression of LTP. We conclude that presynaptic LTP in bursting cells requires activation of PKA by a calcium-dependent adenylyl cyclase while LTP in regular firing cells is independent of elevated cAMP levels. Our results provide evidence for a differential role of cAMP in LTP at hippocampal output synapses.
Key words: bursting; cAMP; forskolin; LTP; subiculum; hippocampus
Received Oct. 15, 2008;
accepted Nov. 4, 2008.
Correspondence should be addressed to either of the following: Christian Wozny at his present address: Medical Research Council Laboratory of Molecular Biology, Hills Road, Cambridge CB2 OQH, UK, Email: cwozny{at}mrc-lmb.cam.ac.uk; or Dietmar Schmitz, Neuroscience Research Center, Charité–Universitätsmedizin Berlin, Charitéplatz 1, 10117 Berlin, Germany, Email: dietmar.schmitz{at}charite.de